Tim-3在强直性脊柱炎中的表达及肾痹汤的临床疗效观察
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摘要
目的:通过半定量PCR、流式细胞技术分析强直性脊柱炎(AS)患者与健康对照者PBMC中Tim-3、Galecin-9及其他相关细胞因子的表达差异,为进一步阐明AS的发病机制及Tim-3与AS的关系奠定基础。方法:在山东大学齐鲁医院风湿内科及山东省中医院风湿科选强直性脊柱炎患者55例,提取PBMC,PCR检测其表面TNF-α及Gal-9的相对表达量,流式细胞仪检测T细胞表面Tim-3表达。结果:Tim-3在AS患者外周血各T细胞亚群(CD4+T、CD8+T)的表达率均显著高于健康对照。(AS患者vs健康对照:CD4+T 2.32±2.25%vs1.44±1.40%; CD8+T 16.92±8.36%vs12.03±5.71%;P﹤0.05);经治疗后AS患者外周血PBMC细胞上Gal-9表达与PBMC TNF-αmRNA水平呈正相关(r=0.47,p<0.05);AS患者外周血各T细胞亚群(CD4+T、CD8+T)Tim-3、Gal-9的表达水平与疾病活动度指标BASDAI无明显相关。结论:本研究首次证实AS患者Tim-3分子较正常对照表达增高,且gal-9在治疗过程中的表达升高,表明Tim-3/gal-9可能成为AS诊断和治疗的新靶点。
第二部分临床观察
目的:观察中药肾痹汤方联合西药对活动期强直性脊柱炎患者临床疗效。方法:病例数40例,其中20例来自齐鲁医院,为对照组,20例来自山东省中医院,为观察组。对照组:单纯西药治疗:NSAIDS+柳氮磺吡啶+沙利度胺。实验组:在上述西药(除沙利度胺)同时加用以肾痹汤为原方加减的中药汤剂,观察临床疗效。疗程为3个月。结果:观察组患者BASDAI指数、PGA、ESR治疗前与治疗后比较有差异有统计学意义(BASDAI:5.10±1.64vs2.76±1.16,P<0.05;PGA:5.85±1.57vs3.35±1.37,P<0.05;ESR:57.40±28.93vs18.00±12.43;P<0.05);对照组患者BASDAI、PGA、ESR治疗前与治疗后比较差异有统计学意义(BASDAI:5.52±1.65vs2.28±1.23,P<0.05;PGA:6.00±1.81vs3.00±1.69,P<0.05;ESR:66.70±27.45vs18.55±18.01,P<0.05);BASDAI指数、PGA、ESR两组治疗前后差值比较差异无统计学意义(BASDAI:2.34±1.77vs3.24±2.12,P>0.05;PGA:2.50±1.67vs3.00±2.85,P>0.05;ESR:39.40±29.85vs48.15±27.71,P>0.05)。结论:两组观察临床疗效无明显差异,观察组无明显不良反应。
Objective: To study the expression of Tim-3 and Gal-9 on the cell subsets of peripheral blood mononuclear cells (PBMC) in AS patients as to further spelled out the mechanism of AS.Methods: 55 AS patients from Qilu Hospital and Shandong Hospital of TCM were enrolled in this researeh. The relative expression of TNF-αand Gal-9 on PBMC were measured by PCR while Tim-3 by flow cytometry.Result: More large proportion of Tim-3+ cells was detected on CD4+T cells (2.32±2.25%vs1.44±1.40%,p<0.05) CD8 + Tcells (16.92±8.36%vs12.03±5.71%,P﹤0.05 ) in patients with AS than that of healthy controls. The expression levels of Gal-9 on PBMC of AS patients after treatment positively correlates with that of TNF-α(r=0.47,p<0.05). Tim-3 on the subsets of T cells and Gal-9 on PBMC have no obvious correlation with BASDAI. Conclution: Tim-3 is first confirmed as over-expressed compared to the normal control,furthermore,gal-9 induced after treatment,that indicated that Tim-3/gal-9 might be a new target for diagnosising and treating .
Part two Clinical research
Objective: Research the prescription of ShenBi Decoction combined with western medicine on the clinical effectiveness in patients with AS in acute stage.Methods: 20 patients with AS from Shandong Hospital of TCM were sorted to experimental group while another 20 ones from Qilu Hosipital were sorted to control group.Control group is given NSAIDs,Sulfasalazine and Thalidomide;experiment group is given above-mentioned western medicine except Thalidomide combined with prescription of ShenBi Decoction.The clinical effectiveness is observed after 3 months.Results: After treatment,the BASDAI,PGA and ESR were improved significantly both in the two groups.The comparison results of the difference before and after treatment about the observed group and the controlled group were BASDAI:2.34±1.77vs3.24±2.12,P>0.05;PGA:2.50±1.67vs3.00±2.85,P>0.05;ESR:39.40±29.85vs48.15±27.71,P>0.05.Conclution: The therapeutic efficacy of conventional therapy of western medicine cooperated with traditional Chinese medicine of ShenBi Decoction in treating active AS is not superior to conventional therapy of western medicine,but the former has fewer side effects than the latter obviously.
第二部分临床观察
目的:观察中药肾痹汤方联合西药对活动期强直性脊柱炎患者临床疗效。方法:病例数40例,其中20例来自齐鲁医院,为对照组,20例来自山东省中医院,为观察组。对照组:单纯西药治疗:NSAIDS+柳氮磺吡啶+沙利度胺。实验组:在上述西药(除沙利度胺)同时加用以肾痹汤为原方加减的中药汤剂,观察临床疗效。疗程为3个月。结果:观察组患者BASDAI指数、PGA、ESR治疗前与治疗后比较有差异有统计学意义(BASDAI:5.10±1.64vs2.76±1.16,P<0.05;PGA:5.85±1.57vs3.35±1.37,P<0.05;ESR:57.40±28.93vs18.00±12.43;P<0.05);对照组患者BASDAI、PGA、ESR治疗前与治疗后比较差异有统计学意义(BASDAI:5.52±1.65vs2.28±1.23,P<0.05;PGA:6.00±1.81vs3.00±1.69,P<0.05;ESR:66.70±27.45vs18.55±18.01,P<0.05);BASDAI指数、PGA、ESR两组治疗前后差值比较差异无统计学意义(BASDAI:2.34±1.77vs3.24±2.12,P>0.05;PGA:2.50±1.67vs3.00±2.85,P>0.05;ESR:39.40±29.85vs48.15±27.71,P>0.05)。结论:两组观察临床疗效无明显差异,观察组无明显不良反应。
Objective: To study the expression of Tim-3 and Gal-9 on the cell subsets of peripheral blood mononuclear cells (PBMC) in AS patients as to further spelled out the mechanism of AS.Methods: 55 AS patients from Qilu Hospital and Shandong Hospital of TCM were enrolled in this researeh. The relative expression of TNF-αand Gal-9 on PBMC were measured by PCR while Tim-3 by flow cytometry.Result: More large proportion of Tim-3+ cells was detected on CD4+T cells (2.32±2.25%vs1.44±1.40%,p<0.05) CD8 + Tcells (16.92±8.36%vs12.03±5.71%,P﹤0.05 ) in patients with AS than that of healthy controls. The expression levels of Gal-9 on PBMC of AS patients after treatment positively correlates with that of TNF-α(r=0.47,p<0.05). Tim-3 on the subsets of T cells and Gal-9 on PBMC have no obvious correlation with BASDAI. Conclution: Tim-3 is first confirmed as over-expressed compared to the normal control,furthermore,gal-9 induced after treatment,that indicated that Tim-3/gal-9 might be a new target for diagnosising and treating .
Part two Clinical research
Objective: Research the prescription of ShenBi Decoction combined with western medicine on the clinical effectiveness in patients with AS in acute stage.Methods: 20 patients with AS from Shandong Hospital of TCM were sorted to experimental group while another 20 ones from Qilu Hosipital were sorted to control group.Control group is given NSAIDs,Sulfasalazine and Thalidomide;experiment group is given above-mentioned western medicine except Thalidomide combined with prescription of ShenBi Decoction.The clinical effectiveness is observed after 3 months.Results: After treatment,the BASDAI,PGA and ESR were improved significantly both in the two groups.The comparison results of the difference before and after treatment about the observed group and the controlled group were BASDAI:2.34±1.77vs3.24±2.12,P>0.05;PGA:2.50±1.67vs3.00±2.85,P>0.05;ESR:39.40±29.85vs48.15±27.71,P>0.05.Conclution: The therapeutic efficacy of conventional therapy of western medicine cooperated with traditional Chinese medicine of ShenBi Decoction in treating active AS is not superior to conventional therapy of western medicine,but the former has fewer side effects than the latter obviously.
引文
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[2] Sui L,Zhang W,Chen Y,etal.Human membrane protein Tim-3 facilitates hepatitis A virus entry into target cell [J]. Int J Mol Med,2006,17 (6):109321099.
[3]孟景红.细胞因子IL-17和IL-4及Tc1/Tc2失衡在强直性脊柱炎发病中的作用[D].石家庄:河北医科大学,2007。
[4] Yang L,Anderson DE, Kuchroo J, et al,Lack Lack of TIM-3 immuno- regulation in multiple Sclerosis[J]. J Immunol.2008:180(7):4409-14.
[5] Simmons WJ,Koneru M,Mohindru M,et al.Tim-3+T-bet+tumor-specific Th1 cells colocalize with inhibit development and growth of murine neoplasms [J]. J Immunol. 2005:174:1405-1415.
[6] Ying Liu ,Qiang Shu , Lifen Gao, Nan Hou, Di Zhao, et al. Increased Tim-3 expression on peripheral lymphocytes from patients with rheumatoid arthritis negatively correlates with disease activity [J]. Clinical Immunology,(2010),27:1-8.
[7] Chae SC,Park YR,Lee YC,et al.The association of TIM-3 gene polymorphism wiTh atopic disease in Korean population [J].Hum Immunol,2004,65(12):1427-1431.
[8] Chae SC,Park YR,Shim SC,et al.The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis [J].Immunol Lett,2004,95(1):91-96.
[9] Wang Y, Meng J, Shu Q et al. Expression of human TIM-1 and TIM-3 on lymphocytes from systemic lupus erythematosus patients[J]. Scand J Immunol, (2008)67:63—70.
[10] Xia Li, Guojiang Chen , Yurong Li, Renxi Wang, et al. Involvement of T cell Ig Mucin-3 (Tim-3) in the negative regulation of inflammatory bowel disease [J]. Clinical Immunology (2010) 134, 169–177.
[11]马桂琴,冯兴华.AS证候规范化研究初探.中国医药学报,2003,18(12):732-733
[12]郑筱萸.《中药新药临床研究指导原则》.北京:中国医药科技出版社,2002年,第1版:119一12
[13]何清湖.传世藏书·子库·医部·素问.海口:海南国际新闻出版中心,第1版,1995:33
[14]林佩琴.类证治裁.上海:上海科学技术出版社,1962年,第l版:323
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